Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immunodeficiency syndrome (AIDS). This project's long term objective is to study the action of the HIV-1 protease so as to develop specific protease inhibitors which might be able to halt the viral replication. This study is possible only with the availability of large quantities of biologically active HIV-1 protease. This phase I proposal specifically aims to develop a recombinant DNA system to produce the protease. The approach to be used will involve the assembly of a synthetic gene coding for the HIV-I protease. The gene will be cloned into a plasmid and expressed in E. coli. Production level of the gene product will be optimized so that the protease can be economically produced. High level expression of the protease will enable phase II research to focus on the E. coli fermentation scale-up, purification and renaturation of the protease to yield biologically active HIV-I protease.